Principle of Toxicology previous years examinations

2023 exam

1. Philosophy of science

How science is different from pseudoscience and other forms of knowledge-seeking can be defined by the hallmarks of scientific inquiry. Name three of these hallmarks (1.5 p)

1. Transparency: Scientific methods and data are openly shared for review and scrutiny by others.
2. Testability: Scientific claims can be tested through experiments and observations to confirm their validity.
3. Reproducibility: Scientific results can be consistently replicated by others using the same methods and conditions.

Points from slides and extend by ChatGPT

2. Target organs

What defines a target organ within the area of toxicology? Give an example and one reason why this organ can be a target organ.

Defination of target organ*:
Most chemicals that cause harm to the body don't affect all organs equally; instead, they mainly damage one or two specific organs, called the target organs of toxicity.
Liver can be a target organ to serveral toxics as it has high metabolic capacity.

*: Definition from text book page 30, simplified by ChatGPT

3. TK and TD

Briefly define what toxicokinetics and toxicodynamics of a chemical describe.

1. Toxicokinetics refers to how the body handles chemicals, including their absorption, distribution, metabolism, and excretion (ADME), and it determines the concentration of the toxicant at the target site.
2. Toxicodynamics describes how chemicals interact with the body, focusing on processes like binding, interaction, or induction of receptors, and it determines the resulting toxic effects.

Points from slides and combined by ChatGPT

4. Metabolism

The metabolism of exogenous compounds can be divided into phase 1 and phase 2 reactions. What is the function of these two different phases of metabolism? Specify the function of each.

Phase 1 metabolism involves the modification of exogenous compounds through processes like oxidation, reduction, and hydrolysis. These reactions expose or introduce functional groups such as –OH, –NH2, –SH, or –COOH, which increase the compound’s polarity, helping facilitate its elimination by lowering membrane permeability and reducing the likelihood of reabsorption.

Phase 2 metabolism involves conjugation reactions, where the compound or its Phase 1 metabolites are attached to molecules like glucuronic acid or glutathione. This further increases the compound’s polarity, making it more water-soluble and easier to excrete, by adding an ionizable group that significantly decreases membrane permeation.

Information from text book page 198, summarized by ChatGPT

5. Metabolism

Glutathione transferase substrates share two common properties. Which are they?

1.they are hydrophobic
2.they contain an electrophilic atom

3.they react nonenzymatically with GSH at some measurable rate.

Points from text book page 362

6. Cell death

Briefly explain the differences between apoptotic and necrotic cell death including how they are activated and their biological consequences in vivo.

Necrotic cell death occurs when cells are exposed to extreme physical or chemical damage, causing them to break down uncontrollably. This type of cell death is chaotic and harmful.

Apoptotic cell death, on the other hand, is a controlled process, often part of normal physiological functions or triggered when a cell’s adaptive mechanisms fail. It is regulated by genetic factors, helps maintain organ function, and can aid in development and disease prevention.

Information from slides, simplified by ChatGPT

7. EDCs

Which are the three parts of the definition of an Endocrine Disruptor that also are the basis for the regulatory criteria for identification of Endocrine Disrupters in pesticides?

1. EDCs alter the function of the endocrine system, i.e. have an endocrine mechanism
2. EDCs cause an adverse effect in an intact organism
3. The adverse effect is a consequence of (is caused by) the endocrine mechanism

Answer from Anna

8. Occupational toxicology

Safe and healthy working environments are a fundamental right at work.

Mention two important routes of exposure to toxicants in occupational settings and give one relevant example of toxicant for each route. (1 p)

1. Inhalation: Workers can inhale airborne toxicants, such as crystalline silica dust in quarry work, which can lead to respiratory diseases like silicosis.
   
2. Skin exposure: Toxicants can be absorbed through the skin, such as aromatic amines in hair coloring products used by hairdressers, which have been linked to skin sensitization and increased cancer risk.

Points from slides and extended by ChatGPT

Which disease is the biggest cause for work-related fatalities in the EU? (0.5 p)

Cancer

Point from slides

9. AOPs

What is the basic purpose of the Adverse Outcome Pathway (AOP) paradigm? (1 p)

for the scientific community to collectively develop a useful AOP knowledgebase that encompasses toxicological contexts of concern to human health and ecological risk assessment

From reference paper of slide

Name two important features of a key event (KE) in an AOP. (1 p)

1.Key events (KE) are things you can measure
2.KEs are not ”AOP-specific”

Points from slides

10. Critical effect

Identification of the critical effect in a toxicity study is important for regulatory purposes. Which of the below alternatives is the correct definition of a critical effect? Select one alternative:

• The adverse effect observed at the lowest dose in a study.

• The adverse effect observed at the highest dose in a study.

• The earliest effect observed in a study.

• The most severe effect observed in a study.

Answered myself based on textbook page 139.

11. NOAEL/LOAEL

What does NOAEL and LOAEL stand for, and how are they defined?

NOAEL (No Observed Adverse Effect Level): The highest dose or exposure level of a substance at which no significant adverse effects are observed in the exposed population during a study.

LOAEL (Lowest Observed Adverse Effect Level): The lowest dose or exposure level of a substance at which significant adverse effects are observed in the exposed population during a study. 

Points from Course note and extended by ChatGPT

12. Risk assessment

Which two components are essential in order to produce a health risk assessment of a chemical, and why?

To produce a health risk assessment of a chemical, two essential components are:

1. Toxicity: This refers to the chemical's ability to cause harm or adverse health effects. Understanding the toxicity helps determine how dangerous the chemical is.

2. Exposure: This measures the extent to which individuals come into contact with the chemical, including the dose, duration, and frequency of exposure.

Both components are crucial because risk is a function of both the chemical's toxicity and the level of exposure. A chemical may be highly toxic, but if exposure is minimal, the risk might be low, and vice versa.

Points from slides and extended by ChatGPT

13. 3Rs

What are the 3Rs when discussing alternative methods? Define and describe.

Replace – methods which permit a given purpose to be achieved without conducting experiments or other scientific procedures on animals

Reduce – methods obtaining comparable levels of information from the use of fewer animals in scientific procedures, or for obtaining more information from the same number of animals

Refine - methods which alleviate or minimise potential pain, suffering and distress, and which enhance animal well-being

From slides

14. Toxicity testing

Cell models are often used in toxicity testing. Mark all the correct statements below. Select one or more alternatives:

• Cancer cell lines are characterized by contact-growth inhibition.
• Induced pluripotent stem cells can be used for personalized medicine and drug testing.
• Primary cell have a limited proliferation capacity.
• The choice of cell model should be dependent on the research question.
• 3D cell models are more physiologically relevant and more sensitive to toxicants compared to 2D cell models.

Answer by myself.

15. Toxicity testing

Read the above table and answer the following questions. (The column to the left refers to a 16-day study and the column to the right refers to a 13-week toxicity study in rats and mice).

What was the vehicle in this study? (1 p)

corn oil

From Study plan TUT PDF file

The rodents were observed twice daily. Why did they need to observe them this often? (1 p)

According to OECD Guidance, we need to observe them twice daily for mortality and clinical signs

From OECD Guidance

Hematology analysis was not performed in the 16-day study and not in mice in the 13-week study? Mention two plausible reasons for not including these analyses in all studies, for all species. (1 p)

1. The 16-day study is a preliminary study which aims to find proper dose level for long term study, so the hematology analysis is not neccessary.
2. We cannot get enough blood from mice for hematology analysis.

Answered myself

Why do you think the dose levels are different for the shorter and the longer toxicity study (left versus right part of the table)? (1 p)

The dose levels differ between the shorter and longer toxicity studies because, in the shorter study, doses above 30 mg/kg were found to be lethal. To prevent fatalities and better assess long-term effects, the dose was adjusted in the longer toxicity study.

Answered myself and refined by ChatGPT

In this study there were five dose groups and one negative control group (5 + 1), which is more than standard. Give one advantage and one disadvantage with using more dose groups than the required (3 + 1) (1 p).

Advantage: Using more dose groups allows for more detailed and granular data, leading to a better understanding of dose-response relationships.

Disadvantage: It requires the use of more animals, which may conflict with the 3Rs principle (Replacement, Reduction, and Refinement) aimed at minimizing animal use in research.

Answered myself and refined by ChatGPT

16. Toxicity testing

The adjacent summary table shows the main results from toxicity studies in male and female rats and mice. Answer the following questions.

Liver weight increase was one of the effects in this study and occurred in both rats and mice of both sexes. Which species and sex were most sensitive to this effect? Motivate your answer. (1p)

Male rats and female mice were most sensitive to this effect.

Answered myself.

Also the thymus was affected. Was decreased weight or atrophy most sensitive in the female rats? Motivate your answer. (1 p)

No, as the decrease of Platetlet counts and decrease of total T4 concentration shows lower LOAEL.

Answered myself.

What was the NOAEL for male mice? (both sexes were given 0, 0.1, 1, 3, 10 and 30 mg/kg/day). (0.5 p)

1 mg/kg/day

Answered myself.

What was the NOAEL for the specific chemical tested (for all groups combined)? (0.5 p)

There is no NOAEL for the specific chemical tested.

Answered myself.

17. Epidemiology

Mediterranean dietary (MD) pattern is one of the healthy dietary patterns which is associated with high intakes of plant foods, olive oil, fish, and sea foods, low-to-moderate consumption of milk and dairy products, low consumption of poultry, red and processed meat, and moderate consumption of wine (during meals). Previous studies have shown that the MD pattern may have beneficial effects on chronic diseases, such as cardiovascular diseases. Given the antiinflammatory effects of the Mediterranean diet, it may also have a benefit for the prevention of cancers such as breast cancer.

In a study of 350 incident breast cancer cases and 700 age-matched controls among Iranian women in Isfahan, using a validated food-frequency questionnaire, dietary habits were estimated by a face-to-face interview with a trained nutritionist. To determine the relationship between adherence to the Mediterranean diet and breast cancer, logistic regression analysis in adjusted models were used. Age and energy intake were considered in the first model. In the second model, further adjustments for participants’ education (non-educated/educated), marital status (single/married), menopausal status (premenopausal/postmenopausal), region (rural/urban), family history of breast cancer (no/yes), smoking (non-smoker/smoker), consumption of alcohol (no/yes), physical activity, socioeconomic scores (continuous), and disease history (no/yes) were used. In addition, the final model was adjusted for BMI, to remove the confounding effect of obesity from the relationship between the Mediterranean diet and breast cancer. Furthermore, the analysis of logistic regression was stratified according to menopausal status (premenopausal/postmenopausal).

In this study, a significant inverse association between the Mediterranean diet and breast cancer was observed, after controlling for potential potential confounders [highest tertile vs lowest: odds ratio (OR): 0.43, 95% confidence interval (CI): 0.28–0.67]. When results were stratified by menopausal status, the odds ratio for postmenopausal women was OR: 0.37, 95% CI: 0.23-0.60, while for premenopausal women the odds ratio was OR: 1.94, 95% CI 0.57-6.54. (From Sadeghi et al. Front Nutr 2023)

What type of study is this? (1 p)

Case-control study

Answered myself

What does this study show (what are the results)? (1 p)

This study shows that adherence to the Mediterranean diet is significantly associated with a reduced risk of breast cancer, particularly in postmenopausal women. The odds of developing breast cancer were 57% lower for women in the highest tertile of adherence to the Mediterranean diet compared to those in the lowest tertile (OR: 0.43, 95% CI: 0.28–0.67). When the results were stratified by menopausal status, the protective effect was particularly strong among postmenopausal women (OR: 0.37, 95% CI: 0.23-0.60), while no significant association was observed for premenopausal women (OR: 1.94, 95% CI: 0.57-6.54).

Answered by ChatGPT

Describe one type of potential methodological problem (systematic error) in this study. Motivate your answer. (2 p)

A potential methodological problem in this study could be selection bias. This may occur if the cases (breast cancer patients) and controls were not comparable, such as differences in lifestyle or access to healthcare, which could skew the results and affect the association between the Mediterranean diet and breast cancer.

Answered by ChatGPT

18. Gene-environment interaction

Briefly explain what gene-environment interaction is and give one example of relevance for toxicology. (2 p)

Gene–environment interaction refers to the interplay of genes (and, more broadly, genome function) and the physical and social environment. For example, FLG-dependent differences in dermal uptake of some common chemicals.

Definition from National Human Genome Research institute. Example from slides.

What is the type of plot shown above called? (0.5 p)

Manhattan plots

From original paper in slides

Explain in your own words what the axes and the peaks represent. (1 p)

This Manhattan plots showing FDR-adjusted q-values for genome-wide associations taking possible population stratification into account as well as influential covariates between fraction of MMA in urine. Peaks represent an association.

From original paper in slides.

In GWAS Manhattan plots, genomic coordinates are displayed along the x-axis, with the negative logarithm of the association p-value for each single nucleotide polymorphism (SNP) displayed on the y-axis, meaning that each dot on the Manhattan plot signifies an SNP. Because the strongest associations have the smallest p-values (e.g., 10−15), their negative logarithms will be the greatest (e.g., 15). The different colors of each block usually show the extent of each chromosome.

From Wikipedia

X-Axis (Chromosome Position): This axis displays the position of single nucleotide polymorphism across the chromosomes.
Y-Axis (Statistic Significance): This axis represents the negative logarithm of the p-value associated with the association between each SNP and the disease.
A peak is an association.

From Xiyuan

19. Air pollution

Air pollution is a global environmental challenge that varies significantly in its sources and impacts across different regions of the world. In light of the seminars you listened to during the air pollution day, pick one region of the world and discuss (a) sources of air pollution, (b) methods to measure air pollution, and (c) give one example of impact on human health and (d) propose one strategy to mitigate air pollution and its effects.

South America
(a) Cashew nut roasting (combustion of the cashew nut shell)
(b) Real-time particulate matter monitoring, analyse Polycyclic aromatic hydrocarbons (PAHs) content, and track spread of PM
(c) DNA damage
(d) Organize science popularization activities to make workers, employers and government aware of potential hazards of using cashew nut shell as fuel. Then the workers can obtain protective equipment.

Answered myself.

2022 exam

1. What defines a target organ within the area of toxicology? Give an example and one reason why this organ can be a target organ. (2 p)

Defination of target organ*:
Most chemicals that cause harm to the body don't affect all organs equally; instead, they mainly damage one or two specific organs, called the target organs of toxicity.
Liver can be a target organ to serveral toxics as it has high metabolic capacity.

*: Definition from text book page 30, simplified by ChatGPT

2. Briefly define what toxicokinetics and toxicodynamics describes. (2 p)

1. Toxicokinetics refers to how the body handles chemicals, including their absorption, distribution, metabolism, and excretion (ADME), and it determines the concentration of the toxicant at the target site.
2. Toxicodynamics describes how chemicals interact with the body, focusing on processes like binding, interaction, or induction of receptors, and it determines the resulting toxic effects.

Points from slides and combined by ChatGPT

3. What does NOAEL and LOAEL stand for, and how are they defined? (2 p)

NOAEL (No Observed Adverse Effect Level): The highest dose or exposure level of a substance at which no significant adverse effects are observed in the exposed population during a study.

LOAEL (Lowest Observed Adverse Effect Level): The lowest dose or exposure level of a substance at which significant adverse effects are observed in the exposed population during a study. 

Points from Course note and extended by ChatGPT

4. The metabolism of exogenous lipophilic compounds can be divided into phase 1 and phase 2 reactions. What is the function of these two different phases of metabolism? Specify the function of each. (2 p)

Phase 1 metabolism involves the modification of exogenous compounds through processes like oxidation, reduction, and hydrolysis. These reactions expose or introduce functional groups such as –OH, –NH2, –SH, or –COOH, which increase the compound’s polarity, helping facilitate its elimination by lowering membrane permeability and reducing the likelihood of reabsorption.

Phase 2 metabolism involves conjugation reactions, where the compound or its Phase 1 metabolites are attached to molecules like glucuronic acid or glutathione. This further increases the compound’s polarity, making it more water-soluble and easier to excrete, by adding an ionizable group that significantly decreases membrane permeation.

Information from text book page 198, summarized by ChatGPT

5. Why is it so dangerous to exceed the recommended dosage of paracetamol? Which organ is affected? Describe the mechanism behind this toxicity and the role of phase 1 and phase 2 reactions. Can alcohol influence the toxicity of paracetamol? If so, in which way and why? (3 p)

In normal dosage, most of the paracetamol will occur Glucuronidation and sulfation then become inactive. Small part of parocetamol will be oxidized by CYP2E1 and CYP3A4 and converted into NAPQI, a highly reactive intermediate. NAPQI can be conjugated by Glutathione(GSH) and lose activity. However, after taking too much paracetamol, sulfate and glucuronide are saturated, and more paracetamol is diverted to the cytochrome P450 system to produce NAPQI. In this way, after the glutathione provided by the liver cells is exhausted, the remaining NAPQI reacts with proteins and nucleic acids, causing a large number of liver cell damage and death, clinically leading to acute liver necrosis. Alcohol can enhance the toxicity of paracetamol as it can induce CYP2E1 therefore producing more NAPQI, causing more damage to liver.

From slides and Wikipedia.

Refined version by ChatGPT

Exceeding the recommended dosage of paracetamol is dangerous because it leads to the accumulation of a toxic metabolite called NAPQI (N-acetyl-p-benzoquinone imine), which is normally detoxified by conjugation with glutathione (GSH). Under normal conditions, the majority of paracetamol is metabolized through phase 2 reactions—glucuronidation and sulfation—rendering it inactive. A small fraction undergoes phase 1 metabolism via cytochrome P450 enzymes, mainly CYP2E1 and CYP3A4, forming NAPQI.

At excessive doses, phase 2 pathways become saturated, shifting more paracetamol to the P450 pathway, resulting in increased NAPQI production. Once glutathione stores are depleted, NAPQI binds to liver cell proteins and nucleic acids, causing hepatocellular damage, which can lead to acute liver failure.

Alcohol can exacerbate this toxicity because it induces CYP2E1, increasing NAPQI production. Chronic alcohol use depletes glutathione stores and primes the liver for damage, making paracetamol overdose even more dangerous.

6. A. Briefly describe the two main pathways that can trigger apoptosis. (1 p) B. Explain the biological consequences of necrotic respective apoptotic cell death in vivo? (1 p)

There are two major pathways that lead to apoptosis in mammalian cells referred to as receptor-mediated and mitochondrial pathways, and caspase activation is the hallmark of both pathways. Mitochondrial pathway is initiated by signals for cell death acting directly on mitochondria and stimulate the release of proapoptotic proteins including cyt c, with subsequent activation of procaspase-9 and activation of caspase-3. Receptor-mediated pathway is a receptor-mediated pathway in which activation of caspases, particularly procaspase-8, occurs after ligation of membrane receptors. Procaspase-8 is activated directly from receptor ligation through formation of the death-inducible signaling complex (DISC), and caspase-8 activates caspase-3, which in turn cleaves target proteins leading to apoptosis.

From textbook page 98.

7. Name two toxicological health hazards that are generally considered of specific concern in the regulation of chemicals. In other words, health effects that may lead to a chemical being banned or restricted for use. (1 p)

1. Carcinogenicity: Chemicals that are known or suspected to cause cancer in humans can lead to a chemical being banned or restricted. Regulatory agencies often prioritize reducing exposure to carcinogens to minimize cancer risks.

2. Reproductive and developmental toxicity: Chemicals that can harm reproductive health or cause developmental defects in unborn children are also tightly regulated. Substances that affect fertility or cause birth defects are often restricted to protect vulnerable populations, such as pregnant women and children.

Answered by ChatGPT

8. Briefly explain what gene-environment interaction is and give one example of relevance for toxicology. (2 p)

Gene–environment interaction refers to the interplay of genes (and, more broadly, genome function) and the physical and social environment. For example, FLG-dependent differences in dermal uptake of some common chemicals.

Definition from National Human Genome Research institute. Example from slides.

9. A. Name and briefly describe one characteristic feature of a liganded nuclear receptor. (1 p) B. Briefly describe the mechanism by which xenobiotics can disrupt this feature and cause receptor-mediated toxicity. (1 p)

A. chemical recognition: respond directly through physical association with ligand
B. Xenobiotics can cause receptor-mediated toxicity by binding to specific cellular receptors, mimicking or blocking natural ligands, and disrupting normal signaling pathways. This can lead to abnormal activation or inhibition of physiological processes. For example, xenobiotics that act as agonists may overstimulate receptors, triggering toxic downstream effects, while antagonists can block essential signals, impairing normal cellular function. This disruption of receptor activity can lead to harmful effects, such as altered gene expression, metabolic dysfunction, or cell death, contributing to toxicity.

A. From slides
B. Answered by ChatGPT

10. Explain what OECD Test guidelines and GLP are and why they are important for toxicity testing? (2 p)

The OECD Test guidelines (TGs) are a collection of the most relevant internationally agreed test methods used by government, industry and independent laboratories to determine the safety of chemicals and chemical preparations.
The OECD Principles of Good Laboratory Practice (GLP) set quality standards for the organisation and management of test facilities and for performing and reporting studies. 
OECD Test Guidelines and GLP ensure reliable, standardized toxicity data, allowing global mutual acceptance of results. This avoids duplicative testing, saving a lot of money and time.

Definition of OECD TGs from slides

Definition of GLP from website in slides

Importance summarized by ChatGPT based on information from website in slides

11. Discuss advantages and disadvantages with different predictive models for testing toxicity for risk/safety assessment for humans, including in silico, in vitro and in vivo. Discuss each model. (3 p)

In Silico Models
Advantages: Cost-effective, time-efficient, and able to screen many chemicals quickly; reduces animal testing.
Disadvantages: Limited accuracy for novel compounds and may not model complex biological interactions.

In Vitro Models
Advantages: Provide human-relevant data and reduce animal testing.
Disadvantages: Limited ability to replicate whole-organism responses and may miss long-term effects.

In Vivo Models
Advantages: Comprehensive for studying whole-body responses and metabolism; accepted by regulatory authorities as the gold standard.
Disadvantages: Ethical concerns, high costs, and potential species differences affecting human relevance.

Answered by ChatGPT

12. In question 11 you were asked to briefly discuss disadvantages of traditional models used in testing. Choose two of these limitations and briefly explain how they can be met by the Tox21 strategies for testing. (2 p)

1. Cannot evaluate long-term effects in vitro models: Use 3D in vitro origanotypic models
2. Limited accuracy for novel compounds in silico: Use new Computational approaches such as QSARs and Read-Across

Points from slides

13. What are the 3Rs when discussing “Alternative methods”? Define and describe. (3 p)

Replace – methods which permit a given purpose to be achieved without conducting experiments or other scientific procedures on animals

Reduce – methods obtaining comparable levels of information from the use of fewer animals in scientific procedures, or for obtaining more information from the same number of animals

Refine - methods which alleviate or minimise potential pain, suffering and distress, and which enhance animal well-being

From slides

14. A. What is the basic purpose of the Adverse Outcome Pathway (AOP) paradigm? (1 p) B. Name two important features of a key event (KE) in an AOP. (2 p)

A. for the scientific community to collectively develop a useful AOP knowledgebase that encompasses toxicological contexts of concern to human health and ecological risk assessment

B.
1.Key events (KE) are things you can measure
2.KEs are not ”AOP-specific”

A. From reference paper of slide

B. Points from slides

15. During the research seminars on health effects of air pollution you listened to different presentations on this topic. Pick one presentation or topic that you thought was especially interesting and briefly describe the research question, methodology/models used and what the research results showed. (3 p)

Airpolution in South American

Research question: occupational risk associated with artisanal cashew nut roasting

Methodology/models used: Real-time particulate matter monitorin, analyse Polycyclic aromatic hydrocarbons (PAHs) content, and track spread of PM

Research results: The results of this study suggest that artisanal cashew nut roasting is a hazardous occupation, where exposure causes harmful effects such as genotoxic/cytotoxic on workers' health.

Points from slides and original paper.

16. Briefly describe three properties/abilities of nanoparticles that might increase their toxicity compared to micro sized particles following inhalation? (1.5 p)

1. Size and Inhalation Depth: Nanoparticles have a smaller size, allowing them to be easily inhaled into the deep respiratory tract. This deeper penetration increases the likelihood of harmful effects compared to larger particles that may be trapped in the upper respiratory system.

2. Increased Surface Area and Reactivity: Nanoparticles have a larger specific surface area, making them more chemically reactive. This enhanced reactivity can facilitate interactions with biological tissues and enhance the potential for toxicity, as they are more likely to bind to and carry toxic substances.

3. Longevity and Distribution in the Environment: Nanoparticles can remain suspended in the atmosphere for extended periods, allowing them to travel over long distances. This prolonged presence increases human exposure risk and the potential for toxic effects as they can accumulate in various environments and enter the human body through inhalation.

Information from the internet and summarized by ChatGPT.

17. Below you have a picture of the sustainable development goals. Pick three goals and explain how toxicology can contribute to meeting those goals. (3 p)

Goal 3: Good Health and Well-being
Toxicology assesses the safety of chemicals in food and products, identifying harmful substances and their health effects. This helps establish safety standards, reduce exposure to toxins, and improve overall health outcomes.

Goal 6: Clean Water and Sanitation
Toxicology monitors water quality by studying pollutants and their impacts on health and ecosystems. This informs guidelines for safe drinking water and supports policies aimed at preventing waterborne diseases.

Goal 12: Responsible Consumption and Production
Toxicology evaluates the environmental and health impacts of chemicals in manufacturing and agriculture. By promoting safer alternatives and sustainable practices, it helps industries reduce waste and adopt greener technologies.

Answered by ChatGPT

18. Read the table below and answer the following questions.

A. What does gavage mean? (1 p)

Gavage refers to the practice of feeding a substance (often a liquid or paste) directly into the stomach of an animal or person, typically using a tube. 

Answered by ChatGPT

B. The ideal vehicle is water. What vehicle is used in this study? Why do you think they choose that vehicle? (1 p)

corn oil
The reason they choose that vehicle is because the chemical they studied is dissolved in corn oil.

Answered myself.

C. Why is it important to characterize the material of the cages and the bedding? (1 p)

1. Animal Welfare: Ensures materials do not harm or stress animals, impacting their health.
2. Experimental Consistency: Reduces variability in conditions, enhancing reproducibility of results.
3. Contaminant Monitoring: Identifies potential harmful substances that could interfere with research outcomes.

Answered by ChatGPT

D. In this study there are five dose groups and one negative control group (5 + 1), which is more than standard. Give one advantage and one disadvantage with using more dose groups than required (3 + 1). (1 p)

Advantage: Using more dose groups allows for more detailed and granular data, leading to a better understanding of dose-response relationships.

Disadvantage: It requires the use of more animals, which may conflict with the 3Rs principle (Replacement, Reduction, and Refinement) aimed at minimizing animal use in research.

Answered myself and refined by ChatGPT

19. Some reports indicate that fruit and vegetable consumption is related to endometrial cancer risk. In a study of 832 incident endometrial cancer cases and 846 age-matched controls among Chinese women in Shanghai, using a validated food-frequency questionnaire, dietary habits were estimated by in-person interviews. The response rate among the cases was 84.7% and among the controls 72.6%. Total vegetable consumption was inversely associated with endometrial cancer risk (highest quartile vs lowest: odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.50–0.96). For the highest quartile of fruit intake, the OR= 0.97, 95% CI: 0.72 – 1.31. Odds ratios were adjusted for age, education, menopausal status, years of menstruation, first-degree family history of breast, colorectal, endometrial cancer, oral contraceptives use, number of pregnancies, history of diabetes, BMI, total meat and fish intake and caloric intake. (From Tao et al., British Journal of Cancer 2005).

A. What type of study is this? (1 p)

Case-control study

Answered myself.

B. What does the study show (what are the results)? (1 p)

Vegetable Consumption: Higher vegetable intake is linked to a reduced risk of endometrial cancer (OR = 0.69, 95% CI: 0.50–0.96).

Fruit Consumption: No significant association with endometrial cancer risk (OR = 0.97, 95% CI: 0.72–1.31).

Answered by ChatGPT

C. Mention one type of potential methodological problem (systematic error) in this study. Justify. (2 p)

A potential methodological problem in this study could be selection bias. This may occur if the cases (endometrial
cancer) and controls were not comparable, such as differences in lifestyle or access to healthcare, which could skew the results and affect the association between the fruit, vegetable consumption and endometrial
cancer.

Repeated question

Target organs

What defines a target organ within the area of toxicology? Give an example and one reason why this organ can be a target organ. (2 p)

Defination of target organ*:
Most chemicals that cause harm to the body don't affect all organs equally; instead, they mainly damage one or two specific organs, called the target organs of toxicity.
Liver can be a target organ to serveral toxics as it has high metabolic capacity.

*: Definition from text book page 30, simplified by ChatGPT

TK and TD

Briefly define what toxicokinetics and toxicodynamics of a chemical describe.

1. Toxicokinetics refers to how the body handles chemicals, including their absorption, distribution, metabolism, and excretion (ADME), and it determines the concentration of the toxicant at the target site.
2. Toxicodynamics describes how chemicals interact with the body, focusing on processes like binding, interaction, or induction of receptors, and it determines the resulting toxic effects.

Points from slides and combined by ChatGPT

NOAEL/LOAEL

What does NOAEL and LOAEL stand for, and how are they defined?

NOAEL (No Observed Adverse Effect Level): The highest dose or exposure level of a substance at which no significant adverse effects are observed in the exposed population during a study.

LOAEL (Lowest Observed Adverse Effect Level): The lowest dose or exposure level of a substance at which significant adverse effects are observed in the exposed population during a study. 

Points from Course note and extended by ChatGPT

Metabolism

The metabolism of exogenous compounds can be divided into phase 1 and phase 2 reactions. What is the function of these two different phases of metabolism? Specify the function of each.

Phase 1 metabolism involves the modification of exogenous compounds through processes like oxidation, reduction, and hydrolysis. These reactions expose or introduce functional groups such as –OH, –NH2, –SH, or –COOH, which increase the compound’s polarity, helping facilitate its elimination by lowering membrane permeability and reducing the likelihood of reabsorption.

Phase 2 metabolism involves conjugation reactions, where the compound or its Phase 1 metabolites are attached to molecules like glucuronic acid or glutathione. This further increases the compound’s polarity, making it more water-soluble and easier to excrete, by adding an ionizable group that significantly decreases membrane permeation.

Information from text book page 198, summarized by ChatGPT

Gene-environment interaction

Briefly explain what gene-environment interaction is and give one example of relevance for toxicology. (2 p)

Gene–environment interaction refers to the interplay of genes (and, more broadly, genome function) and the physical and social environment. For example, FLG-dependent differences in dermal uptake of some common chemicals.

Definition from National Human Genome Research institute. Example from slides.

3Rs

What are the 3Rs when discussing alternative methods? Define and describe.

Replace – methods which permit a given purpose to be achieved without conducting experiments or other scientific procedures on animals

Reduce – methods obtaining comparable levels of information from the use of fewer animals in scientific procedures, or for obtaining more information from the same number of animals

Refine - methods which alleviate or minimise potential pain, suffering and distress, and which enhance animal well-being

From slides

AOPs

What is the basic purpose of the Adverse Outcome Pathway (AOP) paradigm? (1 p)

for the scientific community to collectively develop a useful AOP knowledgebase that encompasses toxicological contexts of concern to human health and ecological risk assessment

From reference paper of slide

Name two important features of a key event (KE) in an AOP. (1 p)

1.Key events (KE) are things you can measure
2.KEs are not ”AOP-specific”

Points from slides

Air pollution

Air pollution is a global environmental challenge that varies significantly in its sources and impacts across different regions of the world. In light of the seminars you listened to during the air pollution day, pick one region of the world and discuss (a) sources of air pollution, (b) methods to measure air pollution, and (c) give one example of impact on human health and (d) propose one strategy to mitigate air pollution and its effects.

South America
(a) Cashew nut roasting (combustion of the cashew nut shell)
(b) Real-time particulate matter monitoring, analyse Polycyclic aromatic hydrocarbons (PAHs) content, and track spread of PM
(c) DNA damage
(d) Organize science popularization activities to make workers, employers and government aware of potential hazards of using cashew nut shell as fuel. Then the workers can obtain protective equipment.

Answered myself.

Toxicity testing

Read the table below and answer the following questions.

A. What does gavage mean? (1 p)

Gavage refers to the practice of feeding a substance (often a liquid or paste) directly into the stomach of an animal or person, typically using a tube. 

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B. The ideal vehicle is water. What vehicle is used in this study? Why do you think they choose that vehicle? (1 p)

corn oil
The reason they choose that vehicle is because the chemical they studied is dissolved in corn oil.

Answered myself.

C. Why is it important to characterize the material of the cages and the bedding? (1 p)

1. Animal Welfare: Ensures materials do not harm or stress animals, impacting their health.
2. Experimental Consistency: Reduces variability in conditions, enhancing reproducibility of results.
3. Contaminant Monitoring: Identifies potential harmful substances that could interfere with research outcomes.

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D. In this study there are five dose groups and one negative control group (5 + 1), which is more than standard. Give one advantage and one disadvantage with using more dose groups than required (3 + 1). (1 p)

Advantage: Using more dose groups allows for more detailed and granular data, leading to a better understanding of dose-response relationships.

Disadvantage: It requires the use of more animals, which may conflict with the 3Rs principle (Replacement, Reduction, and Refinement) aimed at minimizing animal use in research.

Answered myself and refined by ChatGPT

Epidemiology

Mediterranean dietary (MD) pattern is one of the healthy dietary patterns which is associated with high intakes of plant foods, olive oil, fish, and sea foods, low-to-moderate consumption of milk and dairy products, low consumption of poultry, red and processed meat, and moderate consumption of wine (during meals). Previous studies have shown that the MD pattern may have beneficial effects on chronic diseases, such as cardiovascular diseases. Given the antiinflammatory effects of the Mediterranean diet, it may also have a benefit for the prevention of cancers such as breast cancer.

In a study of 350 incident breast cancer cases and 700 age-matched controls among Iranian women in Isfahan, using a validated food-frequency questionnaire, dietary habits were estimated by a face-to-face interview with a trained nutritionist. To determine the relationship between adherence to the Mediterranean diet and breast cancer, logistic regression analysis in adjusted models were used. Age and energy intake were considered in the first model. In the second model, further adjustments for participants’ education (non-educated/educated), marital status (single/married), menopausal status (premenopausal/postmenopausal), region (rural/urban), family history of breast cancer (no/yes), smoking (non-smoker/smoker), consumption of alcohol (no/yes), physical activity, socioeconomic scores (continuous), and disease history (no/yes) were used. In addition, the final model was adjusted for BMI, to remove the confounding effect of obesity from the relationship between the Mediterranean diet and breast cancer. Furthermore, the analysis of logistic regression was stratified according to menopausal status (premenopausal/postmenopausal).

In this study, a significant inverse association between the Mediterranean diet and breast cancer was observed, after controlling for potential potential confounders [highest tertile vs lowest: odds ratio (OR): 0.43, 95% confidence interval (CI): 0.28–0.67]. When results were stratified by menopausal status, the odds ratio for postmenopausal women was OR: 0.37, 95% CI: 0.23-0.60, while for premenopausal women the odds ratio was OR: 1.94, 95% CI 0.57-6.54. (From Sadeghi et al. Front Nutr 2023)

What type of study is this? (1 p)

Case-control study

Answered myself

What does this study show (what are the results)? (1 p)

This study shows that adherence to the Mediterranean diet is significantly associated with a reduced risk of breast cancer, particularly in postmenopausal women. The odds of developing breast cancer were 57% lower for women in the highest tertile of adherence to the Mediterranean diet compared to those in the lowest tertile (OR: 0.43, 95% CI: 0.28–0.67). When the results were stratified by menopausal status, the protective effect was particularly strong among postmenopausal women (OR: 0.37, 95% CI: 0.23-0.60), while no significant association was observed for premenopausal women (OR: 1.94, 95% CI: 0.57-6.54).

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Describe one type of potential methodological problem (systematic error) in this study. Motivate your answer. (2 p)

A potential methodological problem in this study could be selection bias. This may occur if the cases (breast cancer patients) and controls were not comparable, such as differences in lifestyle or access to healthcare, which could skew the results and affect the association between the Mediterranean diet and breast cancer.

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